This is a request for 5 years of funding through the K25 Mentored Quantitative Research Scientist Development Award mechanism. The applicant proposes to supplement his significant training and research experience in physics and engineering with a mentored career development program in multimodal neuroimaging of the neurobiological and pharmacological aspects of substance abuse. The applicant's short-term goal is to apply the techniques he has developed with NIRS and fMRI to substance abuse studies, and during this process deepen his knowledge of the neurobiology of substance abuse. The applicant's long-term goal is to establish expertise in the field of substance abuse imaging, to be able to identify pressing problems in the field, and develop corresponding effective imaging techniques to study them. The K25 will help the applicant achieve the short-term goal and serve as a stepping-stone for the long-term goal. The training plan includes one-on-one training sessions with proposed mentors, hands-on research, course work, laboratory visits, attendance at national and international scientific meetings, and training in responsible conduct of research. During the early years of the grant, the applicant will take courses in neuroanatomy, neurobiology and substance abuse. The research component of this proposal is structured to allow the applicant to develop imaging biomarkers of acute smoking effects on the cognitive functions using multiple imaging modalities, including near-infrared spectroscopy and functional MRI. The three experiments outlined in this proposal will target three smoking-related markers: brain activation in prefrontal areas known to be involved with executive function and decision-making; the resting state networks thought to be involved with self-monitoring; and the patterns of brain activation associated with tobacco craving and its reduction through smoking. Studying continuous interactions between these markers and tobacco smoking before, during and after smoking will aid in developing and objectively evaluating new treatments. The new techniques developed by the applicant address confounding signals that have severely curtailed the application of BOLD fMRI to a number of substance abuse studies. They allow uninterrupted smoking to be monitored by NIRS and fMRI. Through these experiments, the applicant will acquire skills in all aspects of clinic research studies and give him experience in the practical issues of human substance abuse studies. The experiments will be performed at the McLean Hospital Brain Imaging Center, which has excellent facilities and staff for performing sophisticated NIRS and fMRI experiments in substance abuse. The integrated training and research plans will equip the applicant to shift his research from technology development to biological and pharmaceutical applications. The proposed mentored training plan will assist the applicant to become an independent investigator developing and applying new imaging techniques and analytical tools to study substance abuse.